ARTICLE

Birth Weight and Cardiac Structure in Children

Benyu Jiang, PhD, Keith M. Godfrey, PhD, Christopher N. Martyn, DPhil, Catharine R. Gale, PhD
MRC Epidemiology Resource Centre, University of Southampton, Southampton, United Kingdom
The authors have indicated they have no nancial relationships relevant to this article to disclose.

ABSTRACT
OBJECTIVE. Epidemiologic studies have shown associations between impaired fetal
growth and risk for coronary heart disease in adults. The underlying mechanisms
are unknown. We investigated whether restricted intrauterine growth affects
cardiac structure.
METHODS. We performed echocardiography on 216 9-year-old children who were

measured previously at birth. The diameter of the coronary left and right main
branches was derived from the widest dimension; total coronary artery diameter
was calculated by adding the diameters of the left and right coronary arteries.
Aortic root diameter, left atrial diameter, left ventricular diameter, left ventricular
outflow tract diameter, and left ventricular mass were measured.
RESULTS. On average, children who had weighed less at birth had a smaller total

coronary artery diameter, aortic root diameter, and left ventricular outflow tract
diameter after adjustment for gender, gestational age, current height and weight,
and maternal height and prepregnant weight. For each SD increase in birth
weight, total coronary diameter rose by 0.10 mm, log aortic root diameter rose by
1.5%, and log left ventricular outflow tract diameter rose by 1.6%.

www.pediatrics.org/cgi/doi/10.1542/
peds.2005-1325
doi:10.1542/peds.2005-1325
Key Words
cohort studies, echocardiography,
epidemiology, fetal growth
Abbreviation
CI condence interval
Accepted for publication Aug 2, 2005
Address correspondence to Catharine R. Gale,
PhD, MRC Epidemiology Resource Centre,
Southampton General Hospital, Southampton,
Hants, SO16 6YD, UK. E-mail: crg@mrc.soton.
ac.uk
PEDIATRICS (ISSN Numbers: Print, 0031-4005;
Online, 1098-4275). Copyright 2006 by the
American Academy of Pediatrics

CONCLUSION. Impaired fetal growth may have long-term effects on cardiac structure.

This may help to explain why adults whose birth weight was low are at greater risk
for coronary heart disease.

PEDIATRICS Volume 117, Number 2, February 2006

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e257

PIDEMIOLOGIC STUDIES IN several countries have

shown that impaired fetal growth is associated with

an increased risk for coronary heart disease in later
life.15 The mechanisms that underlie this relation are
unclear. One possibility may be that poor fetal growth
has effects on cardiac structure that persist into childhood and beyond, increasing the risk for coronary artery
disease.
We used echocardiography to examine a group of 216
children who were aged 9 years and had been measured
at birth. Our aim was to investigate the relation between
birth weight and cardiac chamber, aortic root, and coronary artery diameters.

METHODS
The mothers of the children in this study all had taken
part in an earlier study of nutrition during pregnancy
between April 1992 and June 1993. White women who
were aged 16 years or more and had singleton pregnancies of 17 weeks gestation were recruited during their
first visit to the midwives antenatal booking clinic at the
Princess Anne Maternity Hospital in Southampton, UK;
women who had diabetes and those who had undergone
hormonal treatment to conceive were excluded. There
were routine obstetric data about the pregnancy and
delivery, and anthropometric data on the child were
collected at birth. Gestation was estimated from menstrual history and scan data.6 In total, 559 children were
followed up to the age of 9 months, and these children
form the sampling frame for this study.
When the children approached 9 years of age, we
asked the Community Pediatric Service in Southampton
to write to their parents with an invitation to take part in
an additional follow-up study to investigate the effect of
early growth on the structure and function of the heart
and blood vessels, on cognitive function, and on bone
mass. We chose to study the children at 9 years of age
because measurements of cognitive function made at
this age tend to be stable into adulthood and because we
wanted to measure the children before they reached
puberty. All of the children in the cohort had previously
been flagged on the child health computer at the Central
Health Clinic in Southampton. Letters were sent to all
461 families who were still living in the Southampton
area. Of 461 invited, 216 (47%) attended for anthropometry and echocardiography. The children sat quietly
in a temperature-controlled room (20 2C) for at least
10 minutes. When pulse rate and blood pressure measurements indicated hemodynamic stability, transthoracic echocardiography (Acuson 128 XP and a 3.5-MHz
phased array transducer) was performed by a single
echocardiographer (B.J.) with the child in the left lateral
recumbent position. Two-dimensional, M-mode, and
Doppler echocardiograms were recorded over 5 consecutive cardiac cycles, and measurements were made offe258

JIANG, et al

line. Aortic root diameter, left ventricular diameter, left

atrial diameter, and left ventricular outflow tract diameter were measured. Left ventricular mass was calculated according to American Echocardiography Society
convention. The left main and right coronary arteries
were detected in the short axis of the aortic valve, and
their cavity diameter was derived from the widest dimension.7 Total coronary artery diameter was calculated
by adding the diameters of the left and right coronary
arteries. The decision to measure coronary artery diameter was made after the start of the study, so these
measurements were available for 157 children.
The Local Research Ethics Committee approved the
study, and the children and their mothers gave informed
consent. The investigation conforms with the principles
outlined in the Declaration of Helsinki.
Where necessary, variables were transformed using
logarithms to satisfy statistical assumptions of normality.
We used the 2-sample t test and the Wilcoxon rank-sum
test to examine characteristics of the study participants.
Linear regression was used to examine the relation between birth weight, expressed as SD scores, and cardiac
dimensions. Weight and height measurements made at
the 9-year examinations were adjusted for exact age
using the British 1990 growth reference data,8 obtained
from the Child Growth Foundation.
RESULTS
Characteristics of the 216 children and their mothers are
shown in Table 1. Cardiac dimensions all were significantly smaller in girls. Girls were shorter than boys,
although their weights both at the age of 9 years and at
birth were similar. The children who had an echocardiogram (n 216) did not differ from the nonresponders (n 245) in mean birth weight (P .10).
There were no differences between the first 59 children
examined, whose echocardiogram did not include measurement of coronary artery diameter, and the remaining 157 children in birth weight (P .92) or weight at 9
years (P .27), although they were on average 2 cm
shorter (P .05).
As expected, all cardiac dimensions tended to be
larger in children who were taller or heavier at the age
of 9 years. There were no statistically significant differences in cardiac dimensions according to mothers
social class or her smoking status during pregnancy, but
in univariate analysis, all dimensions tended to be larger
in children whose mother was taller. Children whose
mothers prepregnant weight was higher had, on average, a larger left atrial diameter and left ventricular mass.
We examined the relation between each cardiac dimension and birth weight SD scores in separate multivariate linear regression analyses, adjusting for gender
and gestational age at birth, current height and weight,
and maternal height and prepregnant weight (Table 2).
On average, children who had weighed less at birth had

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TABLE 1 Characteristics of the 216 Study Participants and Their Mothers

Characteristics
Child
Birth weight, mean (SD), kg
Premature, %
Weight at 9 y, kg
Height at 9 y, mean (SD), cm
Total coronary artery diameter, mean (SD), mm
Aortic root diameter, cm
Left atrial diameter, mean (SD), cm
Left ventricular mass, g
Left ventricular outow tract diameter, cm
Left ventricular diameter, cm
Mother
Height, mean (SD), cm
Prepregnant weight, kg
Smoked during pregnancy, %
Social class, %
I/II
III
IV/V

Boys
(n 115)

Girls
(n 101)

3.37 (5.9)
7.8
28.1 (25.731.8)
132.0 (6.0)
4.32 (0.29)
2.23 (2.132.36)
2.47 (0.24)
85 (7697)
1.59 (1.521.66)
1.40 (1.321.44)

3.26 (6.5)
6.9
28.2 (25.131.9)
129.5 (6.2)
4.18 (0.24)
2.11 (2.02.19)
2.34 (0.21)
74 (6674)
1.51 (1.451.59)
1.35 (1.311.40)

163.3 (7.3)
59.0 (54.065.0)
17.4

162.2 (6.1)
59.0 (52.366.5)
25.7

29.2
52.2
18.6

22.0
62.0
16.0

Values are medians (interquartile ranges) unless stated otherwise.

TABLE 2 Results of Separate Multivariate Linear Regression Analyses: Change in Each Cardiac Dimension Per SD Score Increase in Birth Weight
Cardiac Dimension

Change in Cardiac Dimensiona (95% CI),

Adjusted for Gender and Gestation

P Value

Change in Cardiac Dimensiona (95% CI),

Adjusted for Gender, Gestation, Current
Weight and Height, and Maternal
Prepregnant Weight and Height

P Value

Total coronary artery diameter, mm

Left atrium diameter, cm
Aortic root diameter
Left ventricular mass
Left ventricular outow tract diameter
Left ventricular diameter

0.09 (0.03 to 0.15)

0.03 (0.01 to 0.08)
2.9% (1.6% to 4.2%)
8.5% (5.1% to 12%)
3.0% (1.9% to 4.1%)
3.0% (1.8% to 4.1%)

.002
.120
.001
.001
.001
.001

0.10 (0.03 to 0.16)

0.02 (0.06 to 0.02)
1.5% (0.1% to 2.8%)
2.4% (1% to 5.1%)
1.6% (0.5% to 2.7%)
0.9% (1% to 1.9%)

.003
.298
.028
.090
.003
.095

a Expressed

as regression coefcient or, for those cardiac dimensions that had been log-transformed, percentage change.

a smaller total coronary artery diameter, aortic root diameter, and left ventricular outflow tract diameter
after adjustment for gender, gestational age, current size,
and maternal prepregnant size. For each SD increase in
birth weight, total coronary artery diameter increased by
0.10 mm (95% confidence interval [CI]: 0.03 0.16), log
aortic root diameter increased by 1.5% (95% CI: 0.1%
2.8%), and log left ventricular outflow tract diameter
rose by 1.6% (95% CI: 0.5%2.6%). These associations
were similar using birth weight unadjusted for duration
of gestation and in boys and girls and were affected little
by adjustment for systolic or diastolic blood pressure or
by exclusion of 16 children who were born before 37
weeks gestation (data not shown). Figure 1 shows the
relation between coronary artery diameter and birth
weight; the relation remained significant when we omitted the 10 children with birth weight 2.5 kg. There
were no significant associations between birth weight
and left ventricular mass, left ventricular diameter, or
left atrial diameter

FIGURE 1
Mean (standard error) total coronary artery diameter (mm), adjusted for gender, gestational age, current height and weight, and maternal height and prepregnant weight,
according to birth weight.

DISCUSSION
In this study of 9-year-old children, we found that
total coronary artery diameter, aortic root diameter, and
left ventricular outflow tract diameter were significantly
smaller in children who had weighed less at birth, after
adjustment for current body size and for maternal
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prepregnant size. There were no significant associations

between birth weight and left ventricular mass, left ventricular diameter, or left atrial diameter.
One of the limitations of this study was our inability
to follow up all children in the original cohort. This was
partly because some had moved away from the area in
which the original study took place and it was not possible to trace them and partly because some declined to
participate. Mean birth weight, however, was similar in
the groups that did and who did not take part in the
current phase of the study, and we think that it is unlikely that nonresponse or our inability to follow up
children who had moved away will have introduced
bias. Another limitation is that data on total coronary
artery diameter were not available for some of the children in the study: the first 59 to attend the clinic for an
echocardiogram. These children were slightly shorter
than the remaining 157 children who attended the
clinic, but as there was no difference between the groups
in mean birth weight or current weight, it is unlikely
that our findings on the relation between birth weight
and total coronary artery diameter would have been
different had we had complete data on all 216 children.
Echocardiography of normal neonates has shown a
linear increase in aortic root diameter with increasing
birth weight.9 Our findings that children who weighed
less at birth have smaller aortic root diameters after
taking account of current size suggest that restricted
prenatal growth could have persisting effects on the
structure of the heart and great vessels and add to the
evidence on the determinants of aortic root diameter.10
A narrow left ventricular outflow tract diameter has
been linked with vibratory innocent murmurs in normal
children,11,12 but it is unclear whether prenatal effects
on the left ventricular outflow tract and aortic root have
other clinical implications. However, it is possible that
small differences in the mechanical and physical properties of the heart and aortic root in early life have a
disproportionate influence on cardiac risk in adulthood.13 Longitudinal studies are needed, however, to
confirm such a hypothesis.
Echocardiographic studies of the coronary arteries in
healthy children with normal hearts have shown that
diameter increases with weight and height.14,15 Our finding that birth weight was associated with total coronary
artery diameter in 9-year-old children, independent of
current weight and height, suggests that growth during
fetal life may have a lasting effect on coronary artery
size. Experimental evidence that intrauterine influences
can have persisting effects on the coronary circulation
has come from studies of sheep that were made anemic
during fetal life.16 Adult sheep that in utero had been
made anemic by isovolemic hemorrhage for a 10-day
period in late gestation showed greater maximal conductance in the coronary circulation.16 Fetal anemia led to
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JIANG, et al

increased coronary reserve and a greater cardiac functional response to acute hypoxic stress in the adult
sheep.17
Intrauterine influences on the development of the
coronary circulation of human infants could have important implications. People who have a smaller coronary artery diameter have a higher prevalence of atherosclerotic lesions,18 and they are likely to be at
increased risk for luminal occlusion as atherosclerosis
progresses.19 They also have a poorer outcome after cardiac interventions such as angioplasty or coronary artery
bypass surgery,20 perhaps as a result of a higher likelihood of thrombosis in smaller vessels.21 The results of
this study showing that birth weight is an independent
predictor of total coronary artery diameter in children
may help to explain the findings linking low birth
weight and increased risk for coronary heart disease in
adults.15
ACKNOWLEDGMENTS
This study was funded by the Medical Research Council
and Children Nationwide.
We thank the children and their families for help and
the research nurses who collected the data.
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Birth Weight and Cardiac Structure in Children

Benyu Jiang, Keith M. Godfrey, Christopher N. Martyn and Catharine R. Gale
Pediatrics 2006;117;e257; originally published online January 17, 2006;
DOI: 10.1542/peds.2005-1325
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PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly

publication, it has been published continuously since 1948. PEDIATRICS is owned, published,
and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk
Grove Village, Illinois, 60007. Copyright 2006 by the American Academy of Pediatrics. All
rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.

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Birth Weight and Cardiac Structure in Children

Benyu Jiang, Keith M. Godfrey, Christopher N. Martyn and Catharine R. Gale
Pediatrics 2006;117;e257; originally published online January 17, 2006;
DOI: 10.1542/peds.2005-1325

The online version of this article, along with updated information and services, is
located on the World Wide Web at:
/content/117/2/e257.full.html

PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly

publication, it has been published continuously since 1948. PEDIATRICS is owned,
published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point
Boulevard, Elk Grove Village, Illinois, 60007. Copyright 2006 by the American Academy
of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.

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